Cerebrospinal Fluid Concentrations of Biogenic Amines and Corticotropin-releasing Factor in Adolescent Non-human Primates as a Function of the Timing of Adverse Early Rearing

Abstract

Adolescent bonnet macaques nursed as infants by mothers facing unpredictable requirements for food procurement (variable foraging demand, VFD) display persistent neurobiological disturbances. This study examined the long-term neurochemical and behavioral effects of adverse rearing initiated later in infancy than in previous cohorts of subjects to test the hypothesis that the timing of an early adverse experience would influence patterns of biobehavioral outcome. Cisternal cerebrospinal fluid (CSF) monoamine and corticotropin-releasing factor (CRF) concentrations were obtained from 20 bonnet macaques (11 VFD-reared and 9 normally reared controls) approximately 2 years after the end of differential rearing. VFD-reared primates displayed on multiple samplings significantly lower CSF CRF concentrations and higher CSF 5-hydroxyindoleacetic acid (5-HIAA) concentration compared to controls. In the VFD-reared, significant inverse correlations between CRF and all three monoamines were found (5-HIAA, 3-methoxy-4-hydroxyphenethyleneglycol and homovanillic acid), most prominently for 5-HIAA. In controls, but not VFD-reared subjects, CSF CRF was positively correlated with changes in "gregariousness" upon presentation of a fear stimulus. VFD-reared subjects displayed greater baseline hierarchical engagement than controls. In contrast to prior findings, in which rearing under VFD conditions at an earlier age led to increased CSF CRF compared with controls, CSF CRF was lower after later exposure to VFD rearing than in controls. Thus, the timing of exposure to VFD conditions early in life evidently determines whether CSF CRF was found to be elevated or decreased, within the context of increased serotonin metabolism, during the course of primate maturation.